Identification and validation of non-coding RNA-mediated high expression of IQGAP3 in poor prognosis of lung adenocarcinoma

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-01-16 DOI:10.1002/jgm.3664

Ziwei Su, Yang Wang, Jialing Cao, Jie Ma, Guangzhao Wang, Huijuan Ren, Yihan Zhang, Kangliang Sheng, Xueying Zhu, Yongzhong Wang

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Abstract

Background

The primary reason for tumor-related deaths worldwide is lung adenocarcinoma (LUAD). The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is crucial for contributing to tumor initiation and progression. However, the precise function and molecular mechanism of IQGAP3 in LUAD remain unknown. The present study aimed to investigate the expression, prognosis, mechanism and tumor immunity associated with IQGAP3 in LUAD.

Methods

The relationship between IQGAP3 and the poor prognosis of LUAD was analyzed using The Cancer Genome Atlas (TCGA) database. This analysis was further validated on lung cancer tissues and cell lines. The function of IQGAP3 was investigated by silencing it in LUAD cell lines. To predict microRNA (miRNA) and long non-coding RNA associated with IQGAP3, the starBase database was utilized, and the predictions were verified by enhancing the function of miRNA. Finally, the relationship between IQGAP3 and tumor immunity was evaluated using Spearman's correlation analysis.

Results

TCGA database revealed that higher levels of IQGAP3 were associated with advanced tumor stage, N stage and poor prognosis in LUAD patients. To confirm that, we conducted experiments on lung cancer tissues and cell lines and found that silencing IQGAP3 significantly inhibited tumor cell proliferation and migration. The expression of IQGAP3 showed a negative correlation with has-miR-101-3p and has-miR-135a-5p, whereas it showed a positive correlation with GSEC, AC005034.3 and TYMSOS. Furthermore, the introduction of miRNA-mimics into lung cancer cell resulted in a significant inhibition of cancer cell growth and migration. Following that, the level of IQGAP3 showed a positive correlation with the infiltration of immune cells in tumors.

Conclusions

These results reveal that IQGAP3 significantly promotes LUAD progression and could serve as a prognostic biomarker for LUAD. Furthermore, IQGAP3 is most likely regulated by the GSEC/TYMSOS-hsa-miR-101-3p axis and the AC005034.3-hsa-miR-135a-5p axis in LUAD.

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非编码 RNA 介导的 IQGAP3 高表达在肺腺癌不良预后中的识别和验证

背景全球肿瘤相关死亡的主要原因是肺腺癌（LUAD）。致癌基因 IQ motif-containing GTPase activating protein 3 (IQGAP3) 是导致肿瘤发生和发展的关键因素。然而，IQGAP3在LUAD中的确切功能和分子机制仍然未知。本研究旨在探讨 IQGAP3 在 LUAD 中的表达、预后、机制及肿瘤免疫相关性。方法利用癌症基因组图谱（TCGA）数据库分析了IQGAP3与LUAD不良预后之间的关系。该分析在肺癌组织和细胞系中得到了进一步验证。通过在 LUAD 细胞系中沉默 IQGAP3，研究了它的功能。为了预测与IQGAP3相关的微RNA（miRNA）和长非编码RNA，研究人员利用了starBase数据库，并通过增强miRNA的功能验证了预测结果。最后，利用斯皮尔曼相关分析评估了 IQGAP3 与肿瘤免疫之间的关系。结果 TCGA 数据库显示，在 LUAD 患者中，较高水平的 IQGAP3 与肿瘤晚期、N 期和预后不良有关。为了证实这一点，我们对肺癌组织和细胞系进行了实验，发现沉默 IQGAP3 能显著抑制肿瘤细胞的增殖和迁移。IQGAP3 的表达与 has-miR-101-3p 和 has-miR-135a-5p 呈负相关，而与 GSEC、AC005034.3 和 TYMSOS 呈正相关。此外，将 miRNA 模拟物引入肺癌细胞可显著抑制癌细胞的生长和迁移。随后，IQGAP3 的水平与肿瘤中免疫细胞的浸润呈正相关。结论这些结果表明，IQGAP3 能明显促进 LUAD 的进展，可作为 LUAD 的预后生物标志物。此外，在 LUAD 中，IQGAP3 很可能受到 GSEC/TYMSOS-hsa-miR-101-3p 轴和 AC005034.3-hsa-miR-135a-5p 轴的调控。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.